RNA abundance is regulated by balancing transcription and RNA degradation, processes that control the temporal and spatial distribution of cellular RNA. After decapping, 5′ to 3′ RNA degradation is accomplished by Xrn1, a 5′ to 3′ exoribonuclease. In the 3′ to 5′ pathway, RNA degradation is catalyzed by a multisubunit 3′ to 5′ exoribonuclease complex termed the RNA exosome. Three additional exosome subunits, Csl4=EXOSC1, Rrp4=EXOSC2, and Rrp40=EXOSC3, include S1 or KH domains, which are postulated to bind RNA.